1. Field of the Invention
The present invention relates to an ion trap/time-of-flight mass spectrometer in a combination of an ion trap mass spectrometer and a time-of-flight mass spectrometer.
2. Description of the Related Art
Accurate mass measurement is a method for measuring an ion mass at accuracy of 1/106, i.e., a ppm level, by a mass spectrometer and determining an ion's elemental composition based on the measured accurate ion mass. A structure elucidation of a sample molecule is performed from the determined ion's elemental composition. For an unknown component, because a molecular formula can be directly determined, the accurate mass measurement is very effective in making accurate identification and elucidation of the molecular structure. Examples of a mass spectrometer capable of performing the accurate mass measurement are a double-focusing magnetic sector type mass spectrometer and a time-of-flight mass spectrometer called a TOF.
Particularly, the TOF has been developed as, e.g., Q-TOF including two Quadrupole Mass Spectrometers (QMS's) disposed between an ion source and the TOF, and ion trap-TOF in which the TOF is coupled to an ion trap comprising a ring electrode and a pair of end cap electrodes. Those TOF's are able to perform the accurate mass measurement with a usual process for mass spectrum measurement.
One example of Q-TOF is disclosed in JP,A 11-154486 (Patent Reference 1), and one example of ion trap-TOF is disclosed in JP,A 2003-123685 (Patent Reference 2).
In the accurate mass measurement using the TOF, calibration of a measured value obtained by the mass spectrometer (i.e., mass calibration) is required for an improvement of accuracy.
When a slightly-charged ion having a mass M is accelerated under application of an acceleration voltage U, the ion flies in a vacuum at a speed v. The speed v is determined as follows:v=1.39×104√(U/M)  (1)
Assuming now that the time required for the ion to fly through a flight space in the TOF with a length L (meter) is t (seconds), the time t is determined by the following formula (2);t=L/v=L/(1.39×104√(U/M)=k√(M)  (2)where k is a constant specific to the mass spectrometer. Thus, the ion flight time t is in proportion to the root of the mass. In the actual TOF, the relationship between the ion flight time, i.e., the ion detection time t, and the ion mass M is approximated as follows;M=at2+bt+c  (3)where a, b and c are constants. In other words, a second-order relation formula holds between the mass M and the detection time t of the ion. A process for determining the relation formula (3) is the mass calibration.
In the mass calibration, a reference material providing a plurality of ions having known masses is introduced to the TOF for measurement of a mass spectrum. The constants a, b and c in the relation formula (3) can be determined using the detection time t of each of the appeared ions and the known mass value M. Therefore, the reference material capable of providing the ions having the known masses over a wide mass range is used.
After completion of the mass calibration, by measuring an actual sample, a mass MO of a sample ion can be determined from a detection time t0 of the sample ion based on the formula (3). Such a method of performing the mass calibration using the reference material and the measurement of the actual sample independently of each other after the lapse of time required for the mass calibration as a preceding stage is called an external reference method. One example of the external reference method is disclosed in, e.g., JP,A 2001-74697 (Patent Reference 3).
However, the accuracy of mass measurement performed by the external reference method is generally about 100 to 30 ppm (ppm=10−6) at a maximum. This low accuracy is attributable to, e.g., extension and contraction of the TOF flight space L caused by temperature changes around the mass spectrometer, etc. and drifts of the acceleration voltage U, the voltage applied to an electrostatic lens, etc. At a level of such accuracy, the element composition cannot be uniquely determined from the measured accurate mass M.
To determine the element composition with a maximally restricted possibility, the measurement accuracy at a level of 5 ppm or less is required. Ensuring such a level of accuracy requires a sample ion and reference material ions to be introduced to a TOF and measured at the same time. Each of the ions obtained from the reference material has a known mass, and it is referred to as a “lock mass ion”. Such a method is generally called an internal reference method. The internal reference method makes it possible to compensate for a temperature drift, etc. and to perform the measurement with high accuracy at all times. Further, because the internal reference material introduced to an ion source of the TOF together with a sample is not required to provide ions over a wide mass range, selection of the reference material is facilitated. One example of the internal reference method is disclosed in, e.g., JP,A 2001-28252 (Patent Reference 4).
Thus, the internal reference method is a method essential for improving the measurement accuracy. In a TOF having the function of MS/MS measurement, such as Q-TOF including a Quadrupole Mass Spectrometers (QMS) upstream of the TOF, however, the mass calibration based on the internal reference method cannot be employed to measure the accurate mass of a product ion obtained by the MS/MS measurement. The reason is that, when a precursor ion is isolated by the first QMS, the lock mass ion of the reference material introduced together with the sample is discarded by the first QMS and is not introduced to the TOF at the same time as the product ion. In other words, because the lock mass ion is lacked in the mass spectrum of the product ion, it is impossible to perform the accurate measurement using the internal reference method.
Journal of American Society for Mass Spectrometry, 10(1999), 1305–1314 (Non-Patent Reference 1) discloses one example trying to cope with such a problem in a manner described below with attention focused on a precursor ion in the MS/MS measurement.
In advance, the accurate mass measurement of an unknown sample is performed by the ordinary method (i.e., the measurement not including the MS/MS measurement) to determine the accurate mass of an ion to be selected as a precursor ion. Then, the MS/MS measurement is performed on the selected precursor ion (through the steps of ion isolation, CID (Collision-Induced Dissociation), and measurement of product ion), and the mass calibration of the product ion is performed while the precursor ion slightly remaining on a mass spectrum of the product ion is used a lock mass ion.